Abstract

Background: Although still largely unexplored, long non-coding RNAs (lncRNAS) are emerging as an integral functional component of the human transcriptome. LncRNAs are mRNA-like transcripts of at least 200 nucleotides (nts) with no protein-coding capacity. Similar to their protein-coding counterparts, lncRNAs are frequently spliced and polyadenylated, but act at the RNA level. The range of functions described for lncRNAs is extensive, and includes key biological roles in chromatin remodeling, alternative splicing and mRNA degradation. Given their biological functions, dysregulation of lncRNAs is rising as an important feature of many disorders, including malignant transformation. However, the extent of the contribution of differential lncRNA expression to normal lung tissue and lung cancer has not been investigated in a comprehensive manner.

Hypothesis: We hypothesized that lncRNAs are expressed in a lung tissue-specific manner and that non-small-cell lung cancer (NSCLC) exhibits aberrant lncRNA expression patterns.

Methods: Serial Analysis of Gene Expression (SAGE) libraries were used to characterize polyadenylated transcripts in lung tissue compared to a panel of 25 different normal human tissues, and to a cohort of 12 NSCLCs. To generate lncRNA expression profiles, we developed a lncRNA discovery pipeline to map-tag-to-lncRNA matches. To identify differentially expressed lncRNAs we used a permutation test based statistical analysis. Expression pattern in lung tumors were compared to profiles from a variety of cancer types in order to identify lncRNA changes prominent in lung cancer.

Results: Here we show that large-scale expression profiling through SAGE, is an effective resource for investigating the expression pattern of polyadenylated lncRNAs. Applying a novel lncRNA discovery pipeline we reveal extensive, tissue-specific lncRNA expression in normal lung compared to a panel of several different normal human tissues. Importantly, our study reveals that NSCLC demonstrate significantly altered lncRNA expression patterns and identify highly dysregulated transcripts associated with this malignancy as oppose to other types of cancer.

Conclusion: Collectively, our findings support an important role for tissue-specific lncRNAs in lung cancer. Characterization of the functional role of these transcripts will have a considerable impact on our understanding of lung cancer development and progression, and may reveal clinically important biomarkers.